Person: Martínez Gómez, Ana Cristina
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First Name
Ana Cristina
Last Name
Martínez Gómez
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Area
Fisiología
Identifiers
5 results
Search Results
Now showing 1 - 5 of 5
Item Role of endogenous hydrogen sulfide in nerve-evoked relaxation of pig terminal bronchioles(Pulmonary Pharmacology & Therapeutics, 2016) Fernandes, Vítor S.; Recio Visedo, María Paz; López-Oliva Muñoz, María Elvira; Martínez Sainz, María Del Pilar; Fernandes Ribeiro, Ana Sofía; Barahona Gomáriz, María Victoria; Martínez Gómez, Ana Cristina; Benedito Castellote, Sara; Agis Torres, Ángel; Cabañero, Alberto; Muñoz, Gemma M.; García Sacristán, Albino; Orensanz Muñoz, Luis Miguel; Hernández Rodríguez, Medardo VicenteHydrogen sulfide (H2S) is a gasotransmitter employed for intra- and inter-cellular communication in almost all organ systems. This study investigates the role of endogenous H2S in nerve-evoked relaxation of pig terminal bronchioles with 260 μm medium internal lumen diameter. High expression of the H2S synthesis enzyme cystathionine γ-lyase (CSE) in the bronchiolar muscle layer and strong CSE-immunoreactivity within nerve fibers distributed along smooth muscle bundles were observed. Further, endogenous H2S generated in bronchiolar membranes was reduced by CSE inhibition. In contrast, cystathionine β-synthase expression, another H2S synthesis enzyme, however was not consistently detected in the bronchiolar smooth muscle layer. Electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked smooth muscle relaxation. Inhibition of CSE, nitric oxide (NO) synthase, soluble guanylyl cyclase (sGC) and of ATP-dependent K+, transient receptor potential A1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels reduced the EFS relaxation but failed to modify the GYY4137 response. Raising extracellular K+ concentration inhibited the GYY4137 relaxation. Large conductance Ca2+-activated K+ channel blockade reduced both EFS and GYY4137 responses. GYY4137 inhibited the contractions induced by histamine and reduced to a lesser extent the histamine-induced increases in intracellular [Ca2+]. These results suggest that relaxation induced by EFS in the pig terminal bronchioles partly involves the H2S/CSE pathway. H2S response is produced via NO/sGC-independent mechanisms involving K+ channels and intracellular Ca2+ desensitization-dependent pathways. Thus, based on our current results H2S donors might be useful as bronchodilator agents for the treatment of lung diseases with persistent airflow limitation, such as asthma and chronic obstructive lung disease.Item Mechanisms involved in testosterone-induced vasodilatation in pig prostatic small arteries(Life Sciences, 2008) Navarro Dorado, Jorge; Orensanz Muñoz, Luis Miguel; Recio Visedo, María Paz; Bustamante Alarma, Salvador; Benedito Castellote, Sara; Martínez Gómez, Ana Cristina; García Sacristán, Albino; Prieto Ocejo, Dolores; Hernández Rodríguez, Medardo VicenteAims: Testosterone is beneficial to the cardiovascular system due to its direct coronary vasodilatory action and its circulatory deficiency is associated with coronary artery disease (CAD), which has been proposed as an extrinsic risk factor for benign prostatic hyperplasia (BPH). Therefore, the current study investigated the mechanisms involved in the testosterone-induced vasodilatation in pig prostatic small arteries. Main methods: The testosterone vasoactive effects were assessed in small arterial rings mounted in micro- vascular myographs for isometric force recordings. Key findings: Testosterone and the non-aromatizable metabolite 4, 5α-dihydrotestosterone (DHT) evoked a similar concentration-dependent relaxation on noradrenaline (NA)-precontracted rings. Similar responses were obtained in preparations contracted with 60 mM K+-enriched physiological saline solution. Endothelium mechanical removal or pre-treatment with blockers of nitric oxide (NO) synthase, guanylate cyclase, aromatase activity, intracellular androgenic receptor (AR), 5α-reductase, prostanoid synthesis and K+ channels, failed to modify the responses to testosterone. In Ca2+-free 124 mM KPSS, testosterone markedly inhibited in a concentration-dependent manner the contraction curve t °CaCl2. In arteries pretreated with an L-type voltage-activated Ca2+ channels (VOCCs) inhibitor, nifedipine, testosterone still relaxed noradrenaline- precontracted arteries. Significance: These data suggest that testosterone induces a direct vasodilatory action in pig prostatic small arteries independent of either endothelium, NO, prostanoids, aromatase or 5α-reductase activities, AR or K+ channels. Such an effect is suggested to be produced via blockade of extracellular Ca2+ entry through L-type VOCCs and non-L-type Ca2+ channels. Testosterone-induced vasodilatation could be useful to prevent prostatic ischemia.Item Impaired Excitatory Neurotransmission in the Urinary Bladder from the Obese Zucker Rat: Role of Cannabinoid Receptors(Plos One, 2016) Blaha, Igor; Recio Visedo, María Paz; Martínez Sainz, María Del Pilar; López-Oliva Muñoz, María Elvira; Fernandes Ribeiro, Ana Sofía; Agis Torres, Ángel; Martínez Gómez, Ana Cristina; Benedito Castellote, Sara; García Sacristán, Albino; Fernandes, Vítor S.; Hernández Rodríguez, Medardo Vicente; Agustín Guerrero-HernandezMetabolic syndrome (MS) is a known risk factor for lower urinary tract symptoms. This study investigates whether functional and expression changes of cannabinoid CB1 and CB2 receptors are involved in the bladder dysfunction in an obese rat model with insulin resistance. Bladder samples from obese Zucker rat (OZR) and their respective controls lean Zucker rat (LZR) were processed for immunohistochemistry and western blot for studying the cannabinoid receptors expression. Detrusor smooth muscle (DSM) strips from LZR and OZR were also mounted in myographs for isometric force recordings. Neuronal and smooth muscle CB1 and CB2 receptor expression and the nerve fiber density was diminished in the OZR bladder. Electrical field stimulation (EFS) and acetylcholine (ACh) induced frequency- and concentration-dependent contractions of LZR and OZR DSM. ACh contractile responses were similar in LZR and OZR. EFS-elicited contractions, however, were reduced in OZR bladder. Cannabinoid receptor agonists and antagonists failed to modify the DSM basal tension in LZR and OZR In LZR bladder, EFS responses were inhibited by ACEA and SER-601, CB1 and CB2 receptor agonists, respectively, these effects being reversed by ACEA plus the CB1 antagonist, AM-251 or SER-601 plus the CB2 antagonist, AM-630. In OZR bladder, the inhibitory action of ACEA on nerve-evoked contractions was diminished, whereas that SER-601 did not change EFS responses. These results suggest that a diminished function and expression of neuronal cannabinoid CB1 and CB2 receptors, as well as a lower nerve fiber density is involved in the impaired excitatory neurotransmission of the urinary bladder from the OZR.Item Pre‐ and post‐junctional bradykinin B2 receptors regulate smooth muscle tension to the pig intravesical ureter(Neurourology and Urodynamics, 2016) Fernandes Ribeiro, Ana Sofía; Fernandes, Vítor S.; Martínez Sainz, María Del Pilar; López-Oliva Muñoz, María Elvira; Barahona Gomáriz, María Victoria; Recio Visedo, María Paz; Martínez Gómez, Ana Cristina; Blaha, Igor; Orensanz Muñoz, Luis Miguel; Bustamante, Salvador; García Sacristán, Albino; Prieto Ocejo, Dolores; Hernández Rodríguez, Medardo VicenteAims Neuronal and non-neuronal bradykinin (BK) receptors regulate the contractility of the bladder urine outflow region. The current study investigates the role of BK receptors in the regulation of the smooth muscle contractility of the pig intravesical ureter. Methods Western blot and immunohistochemistry were used to show the expression of BK B1 and B2 receptors and myographs for isometric force recordings. Results B2 receptor expression was consistently detected in the intravesical ureter urothelium and smooth muscle layer, B1 expression was not detected where a strong B2 immunoreactivity was observed within nerve fibers among smooth muscle bundles. On ureteral strips basal tone, BK induced concentration-dependent contractions, were potently reduced by extracellular Ca2+ removal and by B2 receptor and voltage-gated Ca2+ (VOC) channel blockade. BK contraction did not change as a consequence of urothelium mechanical removal or cyclooxygenase and Rho-associated protein kinase inhibition. On 9,11-dideoxy-9a,11a-methanoepoxy prostaglandin F2α (U46619)-precontracted samples, under non-adrenergic non-cholinergic (NANC) and nitric oxide (NO)-independent NANC conditions, electrical field stimulation-elicited frequency-dependent relaxations which were reduced by B2 receptor blockade. Kallidin, a B1 receptor agonist, failed to increase preparation basal tension or to induce relaxation on U46619-induced tone. Conclusions The present results suggest that BK produces contraction of pig intravesical ureter via smooth muscle B2 receptors coupled to extracellular Ca2+ entry mainly via VOC (L-type) channels. Facilitatory neuronal B2 receptors modulating NO-dependent or independent NANC inhibitory neurotransmission are also demonstrated. Neurourol. Urodynam. 35:115–121, 2016. © 2014 Wiley Periodicals, Inc.Item Hydrogen sulfide mediated inhibitory neurotransmission to the pig bladder neck: role of KATP channels, sensory nerves and calcium signaling.(Journal of Urology, 2013) Leite Fernandes, Vitor Samuel; Fernandes Ribeiro, Ana Sofía; Barahona Gomáriz, María Victoria; Orensanz Muñoz, Luis Miguel; Martínez Sáenz, Ana; Recio Visedo, María Paz; Martínez Gómez, Ana Cristina; Bustamante, Salvador; Carballido, Joaquín; García Sacristán, Albino; Prieto Ocejo, Dolores; Hernández Rodríguez, Medardo VicentePurpose: Because neuronal released endogenous H2S has a key role in relaxation of the bladder outflow region, we investigated the mechanisms involved in H2S dependent inhibitory neurotransmission to the pig bladder neck. Materials and methods: Bladder neck strips were mounted in myographs for isometric force recording and simultaneous measurement of intracellular Ca(2+) and tension. Results: On phenylephrine contracted preparations electrical field stimulation and the H2S donor GYY4137 evoked frequency and concentration dependent relaxation, which was reduced by desensitizing capsaicin sensitive primary afferents with capsaicin, and the blockade of adenosine 5'-triphosphate dependent K(+) channels, cyclooxygenase and cyclooxygenase-1 with glibenclamide, indomethacin and SC560, respectively. Inhibition of vanilloid, transient receptor potential A1, transient receptor potential vanilloid 1, vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide and calcitonin gene-related peptide receptors with capsazepine, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively, also decreased electrical field stimulation and GYY4137 responses. H2S relaxation was not changed by guanylyl cyclase, protein kinase A, or Ca(2+) activated or voltage gated K(+) channel inhibitors. GYY4137 inhibited the contractions induced by phenylephrine and by K(+) enriched (80 mM) physiological saline solution. To a lesser extent it decreased the phenylephrine and K(+) induced increases in intracellular Ca(2+). Conclusions: H2S produces pig bladder neck relaxation via activation of adenosine 5'-triphosphate dependent K(+) channel and by smooth muscle intracellular Ca(2+) desensitization dependent mechanisms. H2S also promotes the release of sensory neuropeptides and cyclooxygenase-1 pathway derived prostanoids from capsaicin sensitive primary afferents via transient receptor potential A1, transient receptor potential vanilloid 1 and/or related ion channel activation. Keywords: 4-AP; 4-aminopyridine; AM; ATP; ATP dependent K(+); CGRP; COX; CSE; CSPA; Ca(2+) activated K(+); Emax; K(ATP); K(Ca); K(V); KPSS; L-NOARG; MLCP; N(G)-nitro-L-arginine; NO; PACAP; PKA; PSS; TRPA(1); TRPV(1); VOC; VPAC; [Ca(2+)](i); acetoxymethyl ester; adenosine 5′-triphosphate; calcitonin gene-related peptide; capsaicin sensitive primary afferent; cyclooxygenase; cystathionine γ-lyase; hydrogen sulfide; intracellular Ca(2+); maximum response; muscle, smooth; myosin light chain phosphatase; nitric oxide; physiological saline solution; pituitary adenylyl cyclase activating polypeptide; potassium channels; potassium rich PSS; protein kinase A; synaptic transmission; transient receptor potential A1; transient receptor potential vanilloid 1; urinary bladder; vasoactive intestinal peptide receptor; voltage gated Ca(2+); voltage gated K(+).